Since a process for producing a monoclonal antibody by genetic engineering was proposed in 1975 by Koehler and Milstein [Koehler, G., Milstein, C, Nature 256, 495 (1975)], a road has been opened up to supply a large quantity of a monoclonal antibody as a homogeneous antibody, and such monoclonal antibodies have widely been utilized in the medical and biological fields.
Recently, human monoclonal antibodies are provided in human clinical tests, and particularly draw attention in the antitumor-directed medicinal field. However, purified human monoclonal antibodies have an undesirable property as a preparation that they easily aggregate and precipitate in a solution state or at the time of redissolution (restoration) after freeze drying, and development of monoclonal antibody preparations lacking such an undesirable property and being stabilized is desired.
On the other hand, as methods for stabilization of antibodies (immunoglobulins), there have hitherto been proposed a method which comprises adding to a sulfonated immunoglobulin serum albumin, or serum albumin with glycine and/or mannitol (Japanese Patent Publication No. 20965/1987); a method which comprises adding a comparatively large quantity of a polyhydric alcohol (Japanese Laid-Open Patent Publication No. 88197/1988); a method which comprises adding dextran (Japanese Laid-Open Patent Publication No. 225320/1988); etc. However, it is impossible, by these so far proposed methods, to improve sufficiently the above undesirable property in human monoclonal antibody preparations.
The present inventors now found that stability of a human monoclonal antibody preparation, particularly stability against aggregation and precipitation at the time of redissolution after freeze drying of the human monoclonal antibody is remarkably enhanced by compounding a specified small quantity of mannitol to the human monoclonal antibody, and completed this invention.